Received October 10, 2018; Revised December 4, 2018; Accepted December
4, 2018
The Q61R mutation of the NRAS gene is one of the most frequent
driver mutations of thyroid cancer. Tumors with this mutation are
characterized by invasion into blood vessels and formation of distant
metastases. To study the role of this mutation in the growth of thyroid
cancer, we developed a model system on the basis of thyroid epithelial
cell line Nthy-ori 3-1 transduced by a lentiviral vector containing the
NRAS gene with the Q61R mutation. It was found that the
expression of NRAS(Q61R) in thyroid epithelial cells has a
profound influence on groups of genes involved in the formation of
intercellular contacts, as well as in processes of
epithelial–mesenchymal transition and cell invasion. The
alteration in the expression of these genes affects the phenotype of
the model cells, which acquire traits of mesenchymal cells and
demonstrate increased ability for survival and growth without
attachment to the substrate. The key regulators of these processes are
transcription factors belonging to families SNAIL, ZEB, and TWIST, and
in different types of tumors the contribution of each individual factor
can vary greatly. In our model system, phenotype change correlates with
an increase in the expression of SNAIL2 and TWIST2 factors, which
indicates their possible role in regulating invasive growth of thyroid
cancer with the mutation of NRAS(Q61R).
KEY WORDS: thyroid cancer, invasive growth,
epithelial–mesenchymal transition, NRAS(Q61R), SNAIL,
TWIST